Endometriosis, the third leading cause of gynecologic hospitalization in the United States, remains one of the most enigmatic gynecologic pathologies. Defined by the presence of endometrial tissue outside of the uterus, these implants respond to the hormonal cues of the menstrual cycle and "bleed" as they would in the uterus. The consequence is the development of adhesions, scarring, and painful inflammation. Signs and symptoms include dysmenorrhea, dyspareunia, infertility, dysuria, and dyschezia. The effects of the disease can be physically and mentally debilitating with frequent misdiagnoses and limited treatment options. Despite the high morbidity and health care cost associated with endometriosis, its etiology has not been fully delineated, and no modifiable, protective risk factors have been confirmed. Using data on up to 2,000 laparoscopically confirmed incident cases of endometriosis collected from the Nurses Health Study II, an ongoing, prospective cohort study that began when 116,000 women were enrolled in 1989 . 30,000 of whom also provided blood samples in the late 1990s; we propose a study to assess the following hypotheses: a) Women who are more physically active are at lower risk of endometriosis. b) Paradoxically, women who were obese during childhood are at lower risk of endometriosis. c) Women who experienced longer durations of lactational amenorrhea are at lower risk of endometriosis. d) Women with higher plasma levels of testosterone or with lower levels of estradiol or insulin-like growth factors are at lower risk of endometriosis. All analyses will control for other known and suggested risk factors for endometriosis such as menstrual cycle characteristics, oral contraceptive use, and cigarette smoking. e) In addition, we will establish prospective investigation of endometriosis in the Growing Up Today Study . a cohort of daughters of NHSII participants who range in age from 18-23 in 2005. This provides a unique opportunity to lay the groundwork for future prospective investigations that extend our follow-up to the earliest points of endometriosis incidence as these young women have been providing exposure data since 1996. These analyses will provide the first prospective evaluation of physical activity, will be the first to investigate childhood body size or lactational amenorrhea, and will be the first to evaluate the relation between endogenous hormone levels and this important and understudied cause of morbidity among premenopausal women. Establishment of follow-up among our younger cohort will provide resources for the first prospective study of endometriosis among adolescents. [unreadable] [unreadable] [unreadable]